rDNA Copy Number Variation and Methylation During Normal and Premature Aging

Aging Cell, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 24, 2025

ABSTRACT Ribosomal RNA is the main component of ribosome, which essential for protein synthesis. The diploid human genome contains several hundred copies rDNA transcription unit (TU). Droplet digital PCR and deep bisulfite sequencing were used to determine absolute copy number (CN) methylation status individual TU in blood samples healthy individuals. CN ranged from 243 895 (median 469). There was no difference between males females gain or loss with age (15–71 years). a completely unmethylated (0%) lowly methylated (1%–10%) promoter region significantly decreased, whereas higher (11%–100%) increased age. presumably active hypomethylated (0%–10%) varied 94 277 180), independent CN. In contrast, inactive hypermethylated strongly Promoter hypermethylation compensates some extent enormous variation among Patients Werner syndrome, premature aging syndrome displayed same age‐related changes as controls. role modulating factor health disease largely unexplored. particular, very low high may be associated risk.

Language: Английский

---

Hereditary and familial thyroid tumours

Histopathology, Journal Year: 2017, Volume and Issue: 72(1), P. 70 - 81

Published: Dec. 14, 2017

The worldwide incidence of thyroid malignancies has been increasing rapidly. Sensitive imaging modalities and early detection lesions have made cancers the most rapidly in USA 2017 (SEER Cancer Facts, 2017). Clinical awareness potential risk factors, such as inherited cancers, allowed earlier recognition more vulnerable population clusters. Hereditary neoplasms arising from calcitonin‐producing C cells are known familial medullary carcinomas (FMTCs), include well‐documented syndromes multiple endocrine neoplasia IIA or IIB, pure carcinoma syndrome. Familial follicular referred to non‐medullary (FNMTC), cell‐derived carcinoma. Clinicopathological correlations resulted further subclassification FNMTCs into two groups. Among first group found characterised by a predominance non‐thyroidal tumours, including adenomatous polyposis, Cowden syndrome, Werner Carney complex, Pendred second encompasses spectrum papillary with without oxyphilia, renal cell carcinoma, multinodular goitre. Most described being aggressive than sporadic predisposition for lymph node metastasis, extrathyroidal invasion, younger age onset. distinct pathology some these should alert pathologist possible cancer

Language: Английский

---

Differential stem cell aging kinetics in Hutchinson-Gilford progeria syndrome and Werner syndrome

Protein & Cell, Journal Year: 2018, Volume and Issue: 9(4), P. 333 - 350

Published: Feb. 23, 2018

Hutchinson-Gilford progeria syndrome (HGPS) and Werner (WS) are two of the best characterized human progeroid syndromes. HGPS is caused by a point mutation in lamin A (LMNA) gene, resulting production truncated protein product—progerin. WS mutations WRN encoding loss-of-function RecQ DNA helicase. Here, gene editing we created isogenic embryonic stem cells (ESCs) with heterozygous (G608G/+) or homozygous (G608G/G608G) LMNA biallelic knockout, for modeling pathogenesis, respectively. While ESCs endothelial (ECs) did not present any features premature senescence, HGPS- WS-mesenchymal (MSCs) showed aging-associated phenotypes different kinetics. WS-MSCs had early-onset mild aging while HGPS-MSCs exhibited late-onset acute characterisitcs. Taken together, our study compares contrasts distinct pathologies underpinning disorders, provides reliable stem-cell based models to identify new therapeutic strategies pathological physiological aging.

Language: Английский

---

Familial Syndromes Involving Meningiomas Provide Mechanistic Insight Into Sporadic Disease

Neurosurgery, Journal Year: 2018, Volume and Issue: 83(6), P. 1107 - 1118

Published: March 12, 2018

BACKGROUND Delirium is a postoperative neurological morbidity in glioblastoma whose risk factors, incidence, and prognostic implications remain undefined. OBJECTIVE To develop an algorithm using preoperative factors to predict delirium. METHODS Retrospective analysis of 554 consecutive patients (mean age = 61.5 yr; 42% female) undergoing first procedure at our institution 2005 2011. RESULTS Postoperative delirium occurred 7% (n 38). Patients biopsy (10%; n 54) did not experience In resection 500), multivariate logistic regression identified 5 independently predicting delirium: age, chronic pulmonary disease, psychiatric history, bihemispheric tumors, tumor size. We developed score function entitled "GRAD" (Glioblastoma Risk Assessment for Delirium) stratify into categories by assigning point(s) each factor based on the relative magnitude its coefficient. Point totals were summed patient: with 0 2 227) 3 7 221) points designated as low high rates 2% vs 15%, respectively (chi-square; P < .001), model validated separate patient cohort. lengthened hospital stays (P decreased likelihood discharge home was associated survival (4.5 13.4 mo; hazard ratio 1.9 [1.2-2.8]) analysis. CONCLUSION development tumor-specific (bihemispheric tumors size) patient-specific (age, disease) factors. High-risk their families should be counseled preoperatively, this could considered choice resection, monitored closely postoperatively.

Language: Английский

---

Plugged into the Ku-DNA hub: The NHEJ network

Progress in Biophysics and Molecular Biology, Journal Year: 2019, Volume and Issue: 147, P. 62 - 76

Published: March 6, 2019

Language: Английский

---